Biomaterials are used for the repair, replacement, construction or augmentation of hard and soft tissue in response to diseases, trauma and cosmetic enhancement, as well as drug delivery vehicles.
Bioactive glasses are a type of biomaterial which can be used as bone forming materials for hard tissue applications. Typically, the bioactive glasses are based on silica and comprise a high ratio of calcium to phosphorus to promote formation of apatite crystals, as well as calcium and silica ions to act as crystallization nuclei. However, silica-based glasses tend to have slow and incomplete degradation behaviour. Phosphate based glasses are also attracting attention. Phosphorus-based glasses tend to be more soluble than the silica-based glasses. However, they have limited bioactivity in terms of slow mineralization. Recently, bioactive glasses based on borate have gained in popularity due in part to their faster degradation rate and their potential to be fully biodegradable when compared to traditional silicate glasses. Borate-based glasses are made using melt quench techniques involving oxide precursors melted at high temperatures. This has some drawbacks, such as limiting the ability to incorporate temperature sensitive molecules within the glass due to the high processing temperatures, and not allowing full control of resultant glass microstructure, such as porosity, which is important in biomaterials.
The sol-gel technique is an alternative method for glass production requiring lower processing temperatures and energies than melt quench techniques. Although well established for silica-based glasses, sol-gel methods are still relatively unknown for non-silica based glass networks.
Carta et al (J. Mater. Chem, 2009, 19, p. 150-158) describes a sol-gel method for making borophosphate glasses for biomedical applications comprising a non-siliceous phosphate network incorporating boron. The borophosphate glass systems thus produced are described as 40(P2O5)-x(B2O3)-(60-x)(Na2O) (10≤x≥25 mol. %) in which the phosphate is the main glass network former. In the sol-gel method of Carta, precursor solutions of phosphorus pentoxide dissolved in anhydrous ethanol, boric acid in methanol solution, and sodium methoxide in methanol are mixed to obtain a sol. Gelation of the sol is said to take 10 days at room temperature. Potential uses of such borophosphates are cited as including degradable temporary implants e.g. for promoting healing or the growth of the surrounding tissue, as well as drug delivery systems.
WO2014/159240 also describes compositions and methods for manufacturing sol-gel derived bioactive borophosphate glasses for medical applications in which the glass is at least 5 wt % CaO, at least 10 wt % P2O5, at least 10 wt % Na2O, and at least 25 wt % B2O3, and is substantially silica free. The bioactive glass is said to be useful as hemostatic materials, and for stimulating activity of a gene that promotes wound healing and/or bone regeneration. In one example, precursors of triisopropylborate, ethanol and nitric acid are allowed to react before mixing with calcium methoxyethoxide and sodium ethoxide to form a sol. Ethanol and nitric acid are then added to the sol before gelation which takes 24 hours at 60° C. In another example, triethylphosphate and nitric acid are mixed before adding triisopropylborate, calcium methoxyethoxide and sodium ethoxide to form a sol. Ethanol and nitric acid are then added until gelation occurs and this step is maintained at 60° C. for 24 hours to complete the reaction. The compositions thus produced are assumed to have either a phosphate network or a shared phosphate-boron network. It is desired to provide alternative or improved bioactive glass biomaterials and/or methods of manufacture.